HIV infection is associated with functional abnormalities of B lymphocytes, including hypergammaglobulinemia, presence of high numbers of spontaneously activated immunoglobulin-secreting cells in the circulation, and the presence of autoantibodies in serum. The steady, long term activation of B lymphocytes, which seems specific for either HIV determinants or other antigens, might play a crucial role in the pathogenesis of the immune system damage observed during the course of the HIV-induced disease. The objective of this study is the definition of AIDS-associated autoimmune phenomena in the SIV-infected rhesus macaque model. We have tested several uninfected and infected animals for the presence of anti-single stranded (ss) DNA and anti-double stranded (ds) DNA antibodies. In general, anti-ssDNA antibodies are present in a variety of autoimmune diseases and in a few normal individuals, whereas anti-dsDNA antibodies are present in 50% to 70% of patients with systemic lu pus erythematosus (SLE). First, we tested sera from 33 normal and 21 SIV-infected macaques for presence of anti-ssDNA and anti-dsDNA antibodies by ELISA. Second, we tested sera collected from three SIV-infected rhesus macaques prior and at two different time-points after infection. Both anti-ssDNA and anti-dsDNA antibodies are produced by SIV-infected rhesus macaques. The means of the samples (normal versus SIV-infected macaques) are different at the 0.05 level. In the three SIV-infected macaques, anti-DNA antibodies were present at very low level prior to infection. The titers progressively increased following infection. These data demonstrate that infection with SIV triggers the production of anti-DNA antibodies and, therefore, validate the use of SIV-infected rhesus macaques for the study of AIDS-related autoimmune phenomena. To define the mechanisms that lead to the production of these autoantibodies and to test the hypothesis that B cell superantigens are involved in these mechan isms, we are performing a series of experiments, which include the analysis of the effects that recombinant SIV antigens have on B cell activation and expression of cell-surface antigens.